Project Abstract Access to antiretroviral therapy (ART) has been broadly expanded in resource-poor settings, but multiple studies have documented high attrition rates during the period from HIV testing to ART initiation. New evidence-based strategies are needed to safely and effectively streamline ART initiation procedures to improve retention. Among patients with minimal symptoms, multiple studies have demonstrated that same-day HIV testing and ART initiation is associated with superior outcomes, compared with standard care. However, same-day treatment has not been systematically evaluated in patients who present with cough, fever, night sweats, or weight loss, because current tests are not sensitive enough to rule out smear-negative TB. At the end of 2016, the next generation Xpert Ultra test will become commercially available. Ultra has a limit of detection that is 10-fold lower than standard Xpert. If it is demonstrated that Ultra is highly sensitive and has a high negative predictive value for ruling out TB in real-world conditions, then the paradigm for management of smear and Xpert-negative patients could shift to a same-day test, with same-day ART or TB treatment in place of the current standard of care. We propose a randomized trial to compare outcomes with standard and same-day treatment among patients with TB symptoms at HIV diagnosis. The standard group will receive Xpert + Ultra testing with 48-hour results; these tests will be conducted on both spot and early-morning specimens. Those with negative test results will receive standard evaluation, including chest x-ray and a trial of empiric antibiotics, prior to ART initiation. The same-day group will receive Xpert, Ultra testing and chest x-ray with same-day results, and blood draw for routine baseline lab tests. They will receive same- day treatment with either TB medication or ART, based on Day 0 test results. They will return on Day 1 for repeat sputum testing, results of baseline laboratory tests, and for medication changes, if indicated based on test results. Both groups will receive liquid culture as the diagnostic gold standard; those with TB will start ART according to WHO guidelines. Three specific aims are proposed: The first aim is to compare the proportion of participants in the standard and same-day groups who are in care with an undetectable viral load (<200 copies/ml) at 48 weeks after HIV testing. The second aim is to compare mortality in each group at 48 weeks after HIV testing. The third aim is to compare the cost and cost-effectiveness of standard and same-day treatment. If this model of same-day treatment for symptomatic patients is effective, it could serve as a model for other resource-poor settings.